Developmental Screening of Children with Congenital Hypothyroidism Using Ages and Stages Questionnaires Test

Objectives Congenital hypothyroidism (CH) is one of the most common causes of mental retardation in children. We investigated the developmental status of children with CH screened by Ages & Stages Questionnaires (ASQ) measurement scores. Materials & Methods In this retrospective study, neurodevelopmental status of 78 children diagnosed with CH followed up at the Outpatient Pediatric Endocrinology Clinic of Besat Hospital, Hamadan, Iran from May 2006 to Mar 2013, was evaluated by ASQ method. Data on age, sex, birth weight, birth length, head circumference, residency location, parental education level, primary venous TSH and T4 levels, age at diagnosis, treatment start age and initial levothyroxine dosage were extracted from medical records. Data were analyzed using statistical software SPSS. P-value less than 0.05 was considered statistically significant. Results Of the 78 patients, 34 (43.6%) were female, 32 (41%) had developmental disorder, and 56 (71.8%) were living in urban areas. Types of developmental impairments included: global motor delay in 13 (40.6%) patients, problem-solving in 11 (34.3%), impaired communication skills in 5 (15.6%), impaired fine motor skills in 2 (6.2%), and impairment of personal social skills in 1 (3.1%). The average ages for diagnosis and treatment were 25.65 days in patients with developmental impairment and 17.99 days in those without developmental delay. ASQ results showed significant statistical correlation with initial dose of levothyroxine (P=0.017), age of hypothyroidism diagnosis (P=0.002) and age of treatment initiation (P=0.018). Conclusion Early diagnosis and treatment along with initial levothyroxine dose were most important factors of ASQ scores of children with CH. Higher dose of the levothyroxine is required at onset.


Introduction
"Congenital hypothyroidism has been introduced as one of the most common preventable causes of mental retardation which occurs in 1/3000 neonates" (1). Early identification and treatment within 2 wkof age can maintain normal cognitive development (2,3). The physical growth outcome can be evaluated by growth chart (8) and neurodevelopment can be assessed by a wide variety of tests in toddler and preschool-aged child.
Ages & Stages Questionnaires (ASQ) includes developmental screening tests that can help parents check their child's development (9,10). ASQ so far has been translated into many different languages and also recognized as a valid and strong tool for assessing and screening developmental status of children (11). This questionnaire has been translated into Persian in order to adapt it to the Iranian population.
Screening programs of congenital hypothyroidism dramatically improved the neuropsychological outcome in affected children. However, mild impairments in neurocognitive function and intellectual sequel have been reported in some studies of early-treated CH children particularly in those with marked retardation of bone age and/or a low circulating thyroxin before treatment (12)(13)(14)(15).
We aimed to screen the developmental skills of 3 to 5 yr old children with congenital hypothyroidism detected by neonatal screening program in our region. Academy of Pediatrics, T4 < 6.5 µg/dL and TSH > 10 mIU/mL after one month of age was considered as CH (7). Children were diagnosed as permanent CH if they had serum TSH above 10 mIU/L during the first three years of treatment or if they needed LT4 therapy beyond 3 yr of age (TSH rise > 6 mIU/ ml with temporary discontinuation of LT4 after the age of 3 yr (7, 16).

Material & Methods
Those cases lacking necessary data for the current work, and cases that did not have regular follow-up for the first three years of life were excluded from the study. All children at least three years or more and with the criteria of the study were assessed by ASQ method. The patients were divided into three age groups; 3, 4, and 5 yr old.
Ages & Stages Questionnaire is a developmental screening tool to determine whether a child requires further and more comprehensive evaluation/ assessment designed for use by early educators and health care professionals. It has 20 questionnaires that correspond to age intervals from birth to 6 years. If a parent identifies an item as a concern (circles to far right on form), an extra 5 points are scored for that item. Once the total score is calculated, if that score is higher than the cut-off score, the screening results suggest the child should be referred to child development specialist for a developmental checkup.

Statistical analysis
The Chi-square test was employed to analyze qualitative (categorical) variables expressed as ratio and percentages. For analyzing quantitative data, their normality of distribution was assessed based on mean and standard deviations. In order to compare qualitative variables between groups, chi-square test, and Fisher's exact test were used.  Figure 1.
Problem-solving skills was the most frequent type of developmental impairment among female children, while the global motor was the most prevalent one among male children.
Age at diagnosis, initial dose of Levothyroxine (μgr/ kg/d) and mean age at start of T4 supplementation age were the three variables that differed significantly between children with a normal ASQ test and those with an impaired ASQ test.
Comparison of laboratory and treatment-related variables of subjects with normal ASQ score and those with elevated ASQ score are explained in Tables 2 and 3.
Those treated with initial dose LT4 ≤12 µgr/kg/d at diagnosis had a higher ASQ score (impaired) compared with those treated with a dose ≥ 12 μgr/ kg/d (P=0.017) (     of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.